Download A Case Report of Neutrophilic Eccrine Hidradenitis in a Patient

860
NEH in AML—G C Wong et al
A Case Report of Neutrophilic Eccrine Hidradenitis in a Patient
Receiving Chemotherapy for Acute Myeloid Leukaemia
G C Wong,*MBBS, MRCP (UK), M Med (Int Med), L H Lee,**FAMS, MBBS, M Med, Y Y Chong,***FAMS, MBBS
Abstract
Neutrophilic eccrine hidradenitis (NEH) is a neutrophilic dermatosis primarily affecting the eccrine glands and occurs in patients
undergoing chemotherapy. It must be distinguished from infections, drug eruptions, leukaemia cutis or other forms of skin diseases. As
it is self-limiting, establishing the diagnosis will avoid unnecessary treatment for infections or changes in drug therapy.
Ann Acad Med Singapore 1998; 27:860-3
Key words: Eccrine glands, Infection, Malignancy, Neutropenic, Self-limiting
Introduction
Neutrophilic eccrine hidradenitis (NEH) is a neutrophilic dermatosis primarily affecting the eccrine
glands and occurs most commonly in patients undergoing chemotherapy for a malignancy. This was first described by Harrist et al1 in 1982 and Flynn et al2 in 1984.
These cases occurred in men who were receiving
cytarabine-containing induction chemotherapy for acute
myeloid leukaemia (AML). Since then, other drugs such
as bleomycin, 3-5 mitoxantrone, 6,7 chlorambucil, 8
zidovudine9 and acetaminophen 10 have also been
implicated.
As NEH is most frequently seen in patients receiving
chemotherapy, it must be distinguished from disseminated infection, drug hypersensitivity eruptions, leukaemia cutis or other cutaneous metastases, Sweet’s
syndrome, erythema multiforme, vasculitis, bullous
pyoderma and pyoderma gangrenosum.1,2,11,12 Therefore, establishing the diagnosis of NEH is important to
avoid unnecessary treatment for infections or changes in
therapy for non-existent drug reactions.
We describe a patient with AML who developed NEH
on receiving high-dose cytarabine for consolidation
chemotherapy.
Case Report
A 41-year-old man presented with a one-month history of bleeding gums associated with fever, chills and
rigors. He was pancytopenic (haemoglobin 9 g%, total
white (Tw) 2000/cm3, polymorphs 15%, lymphocytes
75%, blasts 7%, platelets (P) 48,000/cm3) and was diagnosed to have AML. He received induction chemotherapy with high-dose cytarabine (1.5 g/m2 for four
days) and idarubicin (12 mg/m2 for two days) and went
into remission.
He then received idarubicin (12 mg/m2 for two days)
and cytarabine (100 mg/m2 for seven days) as the first
consolidation chemotherapy. This was complicated by a
perianal abscess and fistula which were treated with
antibiotics and fistulotomy.
He was next given cytarabine 1.5 g/m2 continuous
infusion for four days as second consolidation chemotherapy. On the second day of the infusion, the patient
developed a generalised maculopapular rash which
was attributed to cytarabine. His full blood count was
normal. The rash resolved with prednisolone. The patient subsequently developed a fever on the third day
and was started on cefuroxime and gentamicin and later
ciprofloxacin. Vancomycin and flagyl were added when
the temperature rose again on day 10. The patient was
neutropenic from day 5 to day 14 post chemotherapy.
Imipenem, amikacin, azithromycin were ordered and
the patient was also started on empiric amphotericin on
day 15. He was on granulocyte-colony stimulating factor (G-CSF) from day 14. On day 16 (Tw 1400 /cm3, P
54%), he became febrile and developed a non-tender,
non-pruritic maculopapular rash with monomorphic
vesicles on the thighs, limbs, neck and trunk (Figs. 1 & 2).
* Registrar
** Consultant
Department of Haematology
*** Consultant
Department of Pathology
Singapore General Hospital
Address for Reprints: Dr G C Wong, Department of Haematology, Singapore General Hospital, 1 Hospital Drive, Singapore 169608.
Annals Academy of Medicine
NEH in AML—G C Wong et al
Fig. 1. Maculopapular rash with vesicles on patient’s forearm and hand.
There was no oro-mucosal lesions. The differential diagnoses included drug eruption and disseminated herpes
infection for which acyclovir was started. A skin biopsy
showed several foci of neutrophils, lymphocytes and
histiocytes associated with nuclear dust in the upper
dermis and few neutrophilic infiltrates within the sweat
ducts (Fig. 3). Mycobacterial, bacterial and fungal cultures were all negative. Tzanck test was also negative.
This was diagnosed as neutrophilic eccrine hidradenitis
on biopsy. The rash subsided over the next four days.
Meanwhile the patient’s counts recovered and he was
discharged two weeks later, well and afebrile. He had
been on regular follow-up and had remained in remission.
Discussion
Neutrophilic eccrine hidradenitis is a neutrophilic
dermatosis primarily affecting the eccrine glands, and
most commonly seen in patients undergoing chemotherapy for treatment of a malignancy. This was first
described by Harrist et al1 in 1982 and Flynn et al2 in 1984.
Drugs implicated include bleomycin,3 mitoxantrone,6
chlorambucil, zidovudine and acetaminophen though
NEH was first attributed to cytarabine.1,2 Malignancies
November 1998, Vol. 27 No. 6
861
Fig. 2. Vesicular rash on back of patient’s neck.
Fig. 3. Skin biopsy showing foci of neutrophils, lymphocytes and histiocytes associated
with nuclear dust in the upper dermis and few neutrophilic infiltrates within the sweat
dusts.
associated with NEH include acute myeloid leukaemia,
acute myelomonocytic leukaemia,1-3 testicular carcinoma,3 Hodgkin’s and non-Hodgkin’s lymphoma and
osteogenic sarcoma. Our patient received high-dose
cytarabine as induction chemotherapy and 1 consolidation therapy with standard dose cytarabine without
862
NEH in AML—G C Wong et al
developing a rash. It was only on second exposure to highdose cytarabine that he developed NEH. This is similar to
a patient reported by Margolis and Gross6 who developed NEH to high-dose cytarabine and not to low-dose
cytarabine. Whether the development of NEH is related
to the dose of chemotherapy or to the number of times of
exposure to the drug has not been reported so far.
Our patient developed the rash when he was neutropenic. This was also seen in patients reported by Bernstein
et al13 and Margolis and Gross.6 Most cases of NEH have
occurred in neutropenic patients, hence this condition is
often regarded by dermatologists to represent a pathologically distinct, benign self-limited drug reaction that
occurs in neutropenic patients.6 However, 1 patient described by Kuttner and Kurban10 did not have a white
blood cell abnormality due to a primary disease or a
drug-induced process. This patient was immunologically
competent and developed NEH after taking acetaminophen. The eruption resolved quickly after the drug
was discontinued. Neutrophilic eccrine hidradenitis may,
therefore, not be restricted to patients with cancer or
neutropenic patients.
Our patient first developed a rash on the second day of
the cytarabine infusion which was attributed to
cytarabine itself. This subsided very quickly. He next
developed a rash on day 16 post chemotherapy.
This proved eventually to be neutrophilic eccrine hidradenitis on biopsy and the rash resolved spontaneously. In the thirteen episodes of NEH reported where
cytarabine was the inciting agent, the rash occurred on
average 9.3 days later. Our patient developed the rash
much later. Four out of eight patients developed a recurrence of the eruption1-3 when the inciting chemotherapeutic agent was readministered. Our patient, however,
only developed NEH on his third exposure to cytarabine.
Our patient was febrile during the episode of NEH.
However, he was neutropenic then and was on antibiotics. Infections and drug rash were considered likely.
Cultures failed to reveal any organisms and biopsy
proved the rash to be due to NEH. Eight patients cited in
the literature were pyrexial at the time of their presentation with NEH. All were receiving chemotherapy for the
treatment of malignancy and were at risk of infection.1,4,6,8,11,12-14 In none of these eight patients was a source
of infection noted. Spontaneous resolution is the rule
with NEH.4 This was also the case in our patient. However, in the patient reported by Bernstein et al,15 the
lesions were painful and their persistence prompted the
use of intravenous corticosteroids. Both the lesions and
fever resolved within 24 hours. Care must be taken in the
decision to give steroids to an already immunocompromised host in such setting.
It has also been reported that leukocyte colony-stimu-
lating factors can induce neutrophilic dermatoses and
necrotizing vasculitis.16 It was observed by Johnson et
al16 that the eruptions consistently developed after 1 to 2
weeks of colony-stimulating factor administration and
that prompt cessation of these factors is often sufficient
for resolution of the rash. Our patient received G-CSF
from day 14 and his rash developed 2 days later on day
16 and resolved over the next 4 days, despite the patient
being still on G-CSF. We feel that the rash is less likely to
be due to G-CSF as it started just 2 days after G-CSF
administration and resolved spontaneously despite continuation of G-CSF.
Neutrophilic eccrine hidradenitis can either present in
a localised distribution involving the limbs or trunk17 or
be generalised.6,9,11 In our patient, the rash was generalised involving the limbs and trunk. There could be a
difference in morphology and distribution and this is
not dependent upon the chemotherapeutic agent administered.15
The true pathophysiological mechanism responsible
for NEH has not been well delineated. Numerous substances have been shown to be chemotactic for neutrophils
such as complement component C5a, hydroxyeicosatetranoic acids (HETE), interleukin 1, platelet
factor and activating factor, platelet-derived growth
factor and others.15 The infiltrate in most specimens was
composed almost entirely of neutrophils, despite the
patients being neutropenic in most of the cases. Hence,
the stimulus attracting the neutrophils to attack the
eccrine glands and coils is very potent.15 It has also been
speculated that this represents a specific drug reaction to
a chemotherapeutic agent.2,12 These agents are believed
to be preferentially secreted in the eccrine coil causing
the neutrophilic response.12 However, there are patients
who manifested NEH only once despite the drug being
used more than once in the treatment regime.
It is also difficult to examine the true incidence of this
disease since it resolves without an alternation in treatment. Therefore, NEH probably represents an underreported benign drug reaction that occurs primarily
with neutropenic patients. It does not appear to be lifethreatening and abates without any changes in drug
therapy.
In conclusion, NEH is a neutrophilic dermatosis seen
most frequently in patients receiving chemotherapy for
the treatment of a malignancy. It occurs most often in
neutropenic patients who may or may not be febrile and
who may be on multiple drugs. Infections and antibiotic
drug rash are the most frequent differentials. Neutrophilic
eccrine hidradenitis should be considered as this is often
self-limiting and non life-threatening and should not
lead to withdrawal of appropriate antibiotics for treatment of infection.
Annals Academy of Medicine
NEH in AML—G C Wong et al
REFERENCES
863
9. Smith K J, Skelton H G III, James W D, Holland T T, Lupton G P, Angritt P.
Neutrophilic eccrine hidradenitis in HIV-infected patients. J Am Acad
Dermatol 1990; 23:945-7.
1. Harrist T J, Fine J D, Berman R S, Murphy G F, Mihm M C Jr. Neutrophilic
eccrine hidradenitis. A distinctive type of neutrophilic dermatosis associated with myelogenous leukemia and chemotherapy. Arch Dermatol
1982; 118:263-6.
10. Kuttner B J, Kurban R S. Neutrophilic eccrine hidradenitis in the absence of
an underlying malignancy. Cutis 1988; 41:403-5.
2. Flynn T C, Harrist T J, Murphy G F, Loss R W, Moschella S L. Neutrophilic
eccrine hidradenitis: a distinctive rash associated with cytarabine therapy
and acute leukemia. J Am Acad Dermatol 1984; 11:584-90.
11. Katsanis E, Luke K-H, Hsu E, Carpenter B F, Mantynen P R. Neutrophilic
eccrine hidradenitis in acute myelomonocytic leukemia. Am J Pediatr
Hematol Oncol 1987; 9:204-8.
3. Fitzpatrick J E, Bennion S D, Reed O M, Wilson T, Reddy V V, Golitz L.
Neutrophilic eccrine hidradenitis associated with induction chemotherapy.
J Cutan Pathol 1987; 14:272-8.
12. Bailey D L, Barron D, Lucky A W. Neutrophilic eccrine hidradenitis: a case
report and review of the literature. Pediatr Dermatol 1989; 6:33-8.
4. Beutner K R, Packman C H, Markowitch W. Neutrophilic eccrine hidradenitis associated with Hodgkin’s disease and chemotherapy: a case report.
Arch Dermatol 1986; 122:809-11.
5. Scallan P J, Kettler A H, Levy M L, Tschen J A. Neutrophilic eccrine
hidradenitis: evidence implicating bleomycin as a causative agent. Cancer
1988; 62:2532-6.
6. Margolis D J, Gross P R. Neutrophilic eccrine hidradenitis: a case report and
review of the literature. Cutis 1991; 48:198-200.
7. Burg G, Bieber T, Langecker P. Lokalisierte neutrophile eccrine Hidradenitis unter Mitoxantron: Eine typische zytostatikanebenwirkung. Hautarzt
1988; 39:233-6 (German) (English abstract).
8. Fernandez Cogolludo E, Ambrojo Antune Z P, Aguilar Martinez A, Pena
Payero M L, Sanchez-Yus-E. Neutrophilic eccrine hidradenitis—a report of
two additional cases. Clin Exp Dermatol 1989; 14:341-6.
November 1998, Vol. 27 No. 6
13. Scherberiske J M, Benson P M, Lupton G P. Asympt erythematous papules
in a leukemic patient. Neutrophilic eccrine hidradenitis. Arch Dermatol
1990; 126:528-32.
14. Scong V Y, Appell M L, Sanders D Y, Omura E F. Annular plaques on the
dorsa of the hands. Arch Dermatol 1991; 127:1398-9, 1400-2.
15. Bernstein E F, Spielrogel R L, Topolsky D L. Recurrent neutrophilic eccrine
hidradenitis. Br J Dermatol 1992; 127:529-33.
16. Johnson M L, Grimwood R E. Leukocyte colony-stimulating factors. A
review of associated neutrophilic dermatoses and vasculitides. Arch
Dermatol 1994; 130:77-81.
17. Hurt M A, Halvorson R D, Petr F C Jr, Cooper J T, Friedman D J.
Eccrine squamous syringometaplasia: a cutaneous sweat gland reaction
in the histologic spectrum of ‘chemotherapy-associated eccrine
hidradenitis’ and ‘neutrophilic eccrine hidradenitis’. Arch Dermatol
1990; 126:73-7.